Fatty-acid amide hydrolase 1

Fatty-acid amide hydrolase 1 or FAAH-1(, oleamide hydrolase, anandamide amidohydrolase) is a member of the serine hydrolase family of enzymes. It was first shown to break down anandamide (AEA), an N-acylethanolamine (NAE) in 1993. In humans, it is encoded by the gene FAAH. FAAH also regulate the contents of NAE's in Dictyostelium discoideum, as they modulate their NAE levels in vivo through the use of a semispecific FAAH inhibitor. The FAAH protein, involved in the metabolism of endocannabinoids, is encoded by the FAAH gene, which also contains the SNP rs324420 (C385A allele), associated with a higher sensitivity of FAAH to proteolytic degradation and a shorter half-life, as compared to the C variant, as the A variant displays normal catalytic properties, but an enhanced sensitivity to the proteolytic degradation, and shorter half-life, leading to increased N-acylethanolamine (NAE) and anandamide (AEA) signaling at the CB1 receptor etc., and which accounts for the protein’s lower amounts seen in high-level performance athletes (i.e., elite athletes), that present an extraordinary interindividual variability of physical, but also mental traits, which greatly influence their sports accomplishments and their career longevity. However, the role of the C385A variant in athletic performance is not consensual, as other evidence suggesting, that the A polymorphism allele genotype is underrepresented in the Polish elite athletes, regardless of metabolic characteristics of their sport disciplines, where it seems to affect the elite athletic performance negatively. FAAH is an integral membrane hydrolase with a single N-terminal transmembrane domain. In vitro, FAAH has esterase and amidase activity. In vivo, FAAH is the principal catabolic enzyme for a class of bioactive lipids called the fatty acid amides (FAAs). Members of the FAAs include: Anandamide (N-arachidonoylethanolamine), an endocannabinoid 2-arachidonoylglycerol (2-AG), an endocannabinoid.

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N-Acylethanolamine

An N-acylethanolamine (NAE) is a type of fatty acid amide where one of several types of acyl groups is linked to the nitrogen atom of ethanolamine, and highly metabolic formed by intake of essential fatty acids through diet by 20:4, n-6 and 22:6, n-3 fatty acids, and when the body is physically and psychologically active,.

Lipid signaling

Lipid signaling, broadly defined, refers to any biological signaling event involving a lipid messenger that binds a protein target, such as a receptor, kinase or phosphatase, which in turn mediate the effects of these lipids on specific cellular responses. Lipid signaling is thought to be qualitatively different from other classical signaling paradigms (such as monoamine neurotransmission) because lipids can freely diffuse through membranes (see osmosis).

Endocannabinoid system

The endocannabinoid system (ECS) is a biological system composed of endocannabinoids, which are endogenous lipid-based retrograde neurotransmitters that bind to cannabinoid receptors (CBRs), and cannabinoid receptor proteins that are expressed throughout the vertebrate central nervous system (including the brain) and peripheral nervous system.

The Molecular Basis for Dual Fatty Acid Amide Hydrolase (FAAH)/Cyclooxygenase (COX) Inhibition

Giulia Palermo

The design of multitarget-directed ligands is a promising strategy for discovering innovative drugs. Here, we report a mechanistic study that clarifies key aspects of the dual inhibition of the fatty acid amide hydrolase (FAAH) and the cyclooxygenase (COX) ...

Wiley-V C H Verlag Gmbh2016

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The Fatty Acid Amide Hydrolase (FAAH) enzyme is a membrane-bound serine hydrolase responsible for the deactivating hydrolysis of a family of naturally occurring fatty acid amides. FAAH is a critical enzyme of the endocannabinoid system, being mainly respon ...

Elsevier2015

Anandamide Hydrolysis in FAAH Reveals a Dual Strategy for Efficient Enzyme-Assisted Amide Bond Cleavage via Nitrogen Inversion

Ursula Röthlisberger, Andrea Cavalli, Pablo Campomanes Ramos, Giulia Palermo

Herein, we combined classical molecular dynamics (MD) and quantum mechanical/molecular mechanics (QM/MM) simulations to unravel the whole catalytic cycle of fatty acid amide hydrolase (FAAH) in complex with anandamide, the main neurotransmitters involved i ...

2015